A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine.  Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact,  preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.

Dr. Michael Mullan M.D., Ph.D
President & CEO
Roskamp Institute
 
 
With Alzheimer’s disease (AD) being the most common type of dementia among the 35 million patients suffering from dementia cases worldwide, the battle to find a drug to at least slow down this disease is becoming more urgent each day. While current medicines do ease the symptoms of AD, none of them delay, stop, or reverse the cognitive and behavioral decline of AD. In recent news, a drug called bapineuzumab, that hoped to improve the cognitive and life functions of the patients participating in the trial, has failed its first of four clinical trials. The 1,100 patients in this late-stage study have mild to moderate cases of Alzheimer’s, and each has a variation of the gene, ApoE4, which increases the chances of developing AD. About half of AD patients have this gene. Bapineuzumab is an antibody based drug that targets beta-amyloid, a protein which scientists believe to be the cause of AD. The failure of this trial may be due to the high risk patients, as well as the fact that the drug is being tested too late into the disease. Jointly created by Pfizer and Johnson & Johnson, it has been announced that Johnson & Johnson will carry out the remaining three clinical trials, with one involving ApoE4 and the other two with patients without the gene. The results of these remaining trials will be presented at a neurology conference in Sweden this September. For more details and news about this study as well as Alzheimer’s disease, please visit:

http://www.washingtonpost.com/business/pfizer-alzheimers-disease-drug-fails-in-1-study-2nd-study-in-different-patients-continues/2012/07/23/gJQAB7K64W_story_1.html

http://www.rfdn.org
http://www.roskampinstitute.us
http://www.michaelmullan.us
http://www.michaelmullangroup.com

Keywords: Alzheimer’s disease; bapineuzumab; ApoE4

Sources: http://www.washingtonpost.com/business/pfizer-alzheimers-disease-drug-fails-in-1-study-2nd-study-in-different-patients-continues/2012/07/23/gJQAB7K64W_story_1.html

http://www.nytimes.com/2012/07/24/business/alzheimers-drug-fails-its-first-clinical-trial.html

You can follow updates on clinical trials at the Roskamp Institute Website: http://www.rfd

Wendy Liu

July 24, 2012